DISCLOSURES Valentin Fuster MD Ph D Honoraria BG
DISCLOSURES Valentin Fuster, MD, Ph. D Honoraria – BG Medicine
Promoting CV & Mental Health: 2010– 2020 Science, Health, Education (SHE) Biological Clinical - From Atheroma to Aging – From CAD to DBD Population – From Risk to Health (3) (3)
CARDIOVASCULAR DISEASE HEART MI BRAIN STROKE Thrombi 1) Emboli 2 2)Thrombi 3)Hemorrh Promoting CV & Mental Health 2010 – 2020
1) Complex Coronary Artery Disease Evidence Base Management TRIAL SYNTAX BARI MVD DM INTERV. HP. Rev Rx + - - + ++ - +- + Data HP-Rev <CABG – HP = ØSx Sc. (Reg)<CABG DM – Int. Sx. Sc. CABG ? HP = INTERV. vs RX <CABG, Sx. Sc Revasc. Rx 42% Largest DB DM HP-Int. Sx. Sc? Rx Approach? FREEDOM Cost, Qo. L ? D Capodanno et. al. AHJ. 2010; 159: 103 (Catania, Italy. ) - Euro. SCORE Refines + + ++ +- +-
TYPE 2 DIABETES – ADJUSTED HAZARD RATIOS FOR ALL-CAUSE MORTALITY AS A FUNCTION OF Hb. A 1 c (N=47970 – UK)1 2. 0 1. 8 HR (95% CI) 2. 0 Yearly mean Mean of all values Updated mean 1. 8 1. 6 1. 4 1. 2 1. 0 0. 8 6. 0 1 2 3 4 5 6 7 Hb. A 1 c (deciles) 1 UK 8 9 10 6. 5 7. 0 7. 5 8. 0 8. 5 9. 0 9. 5 10. 0 10. 5 11. 0 11. 5 Hb. A 1 c (%) General Practice Research Database (1986 -2008) CJ Currie et al. , Lancet 2010; 375: 486 ACCORD – NEJM 2008; 358: 2545 - Intensive targeting of HA 1 c increased mortality
2) Coronary Function Versus Anatomy with Diffuse CAD and Remodeling K Lance Gould JACC: Cardiov. Imaging 2009; 2: 1009.
2)2 Coronary Function (Flow) vs Stenosis (Anatomy) Year Survival Free of Death/MI Clinical Outcomes (Death + MI or MI) FFR-Guided Angio-Guided 730 days 4. 3% “Functionally Complete Revascularization” Intervention of Significant Ischemic lesions and Medical Treatment of Non-Ischemic Ones FAME 2 - TCT 2009 – San Francisco
2)Coronary Function and Anatomic Stenosis Severity Lance Gould JACC: Cardiov. Img 2009; 2: 1009 TF Christian et al. , JACC Img 2009; 2: 1103: MR (3. 0 T)- MBF (Pig)
3) Frequency of X TCFA / Pl. Rupture / Trombus AMI (n=35), SAP (n=20) - 3 -Vessel Optical Coherence Tomography M Masutani et. al. JACC. 2008; 52: 787 (Japan). X TCFA: MI 69%, SAP 10% DEFER (NHJ Pijls et al) JACC 2007; 49: 2105 (Neth. ). DES in <Flow TCFA: No A Tanaka et al EHJ 2009; 30: 1348. Lipid Arch – Decrease Reflow
3) MRI – POST COMPLEX PCI (92) OR CABG (60) Event-free survival (proportions)1 1. 00 0. 75 P=0. 004 0. 50 New HE absent New HE present 0. 25 0. 00 0 10 20 30 40 50 Follow-up duration (months) 1 Death, MI, sustained VT, UA, HF, Cardiac Troponin and LV function post procedure did not alter the independence of HE K Rahimi et al. , Heart 2010 (In Press) (Oxford)
CARDIOVASCULAR DISEASE 1) BRAIN HEART MI Thrombi STROKE 1) Emboli 2 2)Thrombi 3)Hemorrh Promoting CV & Mental Health 2010 – 2020
148 13 146 12 144 11 142 10 140 9 138 8 Mean systolic Blood pressure (mm. Hg) 136 7 Short portable MMSE 134 60 -64 65 -69 70 -74 75 -79 Age Group (yrs) TO Obisecon. Clin Geriatr Med 2009; 25: 259 (NIH) 80 -84 >84 6 SHP-MMSE Mean systolic blood pressure (mm. Hg) 2) ADVANCED AGE, HYPERTENSION AND DEMENTIA SBP AND SHORT PORTABLE MMSE SCORE BY INCREASING AGE GROUPS
2) BLOOD PRESSURE, RISK DEMENTIA – LOGITUDINAL STUDIES Late-Life Hypertension Ueda et al. (1992) Kuusisto et al. (1997) Cuo et al. (1996) Pettiti et al. (2002) Morris et al. (2000) Kokmen et al. (1991) Rockwuud et al. (1996) Mid-Life Hypertension Launer et al. (2000) Kivipelto et al. (2001 b) Wu et al. (2003) Yamada et al. (2003) Whitmer et al. (2005) Late-Life Hypertension Qiu et al. (2003 a) Skoog et al. (1996) Li et al. (2007) Yoshitake et al. (1995) Brayne et al. (1998) Tyas et al. (2001) Posner et al. (2002) Lindsay et al. (2002) Kuller et al. (2003) Borenstein et al. (2005) Petitti et al. (2005) Hypotension Ruitenberg et al. (2001) Morris et al. (2001) Verghese et al. (2003) Nilsson et al. (2007) SP Kennelly, BA Lawlor, RA Kenny. Ageing Research Reviews 2009; 8: 61 TO Obisecon. Clin Geriatr Med 2009; 25: 259 (NIH) – Age, BP, Cognitive Function
SUMMARY OF HYPERTENSIVE THERAPY STUDIES IN ALZHEIMER’S DISEASE Study Year Setting 1994 SHEP Participants and FU 4736 – 4. 5 y Rx/Placebo Diuretic ± β-blocker ± Main Result Rx No significant hypertensive drug 2000 MRC trial 2584 – 3. 9 y Diuretic or β-blocker No significant 2004 SCOPE 4964 – 4. 5 y Candesartan ± Hc. T 3 Significantly less cognitive decline 2003 PROGRESS 6105 – 4. 5 y Perindopril ± indapamide Decreased rates of dementia 2008 Syst-Eur stud 2418 – 2 y Nitrendipine ± enalapril ± Hc. T 3 Decreased risk of dementia by 55% D L Dickstein et al. , Mount Sinai J Med 2010; 77: 103 – 6 Studies on Hypotension
3) Immunohistochemical Stain in a Patient with Alzheimer’s Showing Senile Plaques the Extent of Amyloid Accumulation DP Perl. Mt Sinai J Med. 2010; 77: 32.
3) Amyloid Deposits Make for a Colorful PIB Scan of an Alzheimer’s Patient’s Brain. People with MCI Show Diverse Results G Miller. Science 2009; 326: 386.
3) Mechanisms of Disease: Alzheimer’s Disease More than 35 million people worldwide – 5. 5 million in the United States – have Alzheimer’s disease, a deterioration of memory and other cognitive domains that leads to death within 3 to 9 years after diagnosis. Alzheimer’s is the most common form of dementia, accounting for 50 to 56% of cases at autopsy and in clinical series. Combined with intracerebral vascular disease accounts for another 13 to 17% of cases. The principal risk factor for Alzheimer’s disease is age. Ischemic disease affects 60 to 90% of patients with Alzheimer’s disease. The odds of receiving the diagnosis of Alzheimer’s disease after 85 years of age exceed one in three. As the aging population increases, the prevalence will approach 13. 2 to 16. 0 million cases in the United States by midcentury. An accumulation of misfolded proteins in the aging brain results in oxidative and inflammatory damage, which in turn leads to energy failure and synaptic dysfunction. HW Querfurth, FM La. Ferla. NEJM 2010; 362: 329
3) Role of Vascular Risk Factors and Vascular Dysfunction in Alzheimer’s Disease D L. Dickstein, Ph. D, J Walsh, BA, H Brautigam, BSc, S D. Stockton Jr, BSc, S Ganday, MD, Ph. D, PR. Hof, MD RISK FACTORS Apolipoprotein E Genotype Hypertension Hypotension Cholesterol Diabetes Mellitus Smoking Mount Sinai Journal of Medicine 2010; 77: 82 -102
3) SURVIVAL FOR INCIDENT ALZHEIMER’S DISEASE AND INCIDENT DEMENTIA IN STUDY COHORS (N=819491 MALES ≥ 65 Y – US VA) Dementia Survival probability Alzheimer’s disease 1. 00 0. 99 0. 98 1. 00 0. 98 0. 96 0. 94 0 6 12 18 24 30 36 Angiotensin recept. blockers Lisinopril Cardiovascular comparator 42 48 0. 92 0 Follow-up (months) N-C Li et al. , BMJ 2010; 340: b 5465 6 12 18 24 30 36 42 48
Promoting CV & Mental Health: 2010– 2020 Science, Health, Education (SHE) Biological Clinical - From Atheroma to Aging – From CAD to DBD Population – From Risk to Health (3) (3)
1 -2) RISK FACTORS, BIOIMAGING GENETIC MARKERS, SERUM MARKERS 1 2 2 Genetic Markers Major risk factors 1 Early. Detection Imaging Markers 2 Serum Markers Atherothrombotic disease Cardiovascular events J Sanz, V Fuster, JF Viles-Gonzalez, P Moreno 2010 (In Press)
1) 10 vs 30 -Ys RISK OF HARD CVD FOR 45 -Y. -OLD (5 RF) 30 -y risk 0. 9 0. 8 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0 Abn Lipids ‒ Hypert. ‒ Smoking ‒ Diabetes ‒ 10 -y risk Men Estimated % risk of hard CVD 10 -y risk + ‒ ‒ ‒ + + + ‒ + + 30 -y risk 0. 8 Women 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0 Abn Lipids ‒ Hypert. ‒ Smoking ‒ Diabetes ‒ + ‒ ‒ ‒ Framingham (MJ Pencina et al. ) Circ 2009; 119: 3078 + + ‒ ‒ + + + +
2) HRP –USA Imaging (N = 6000 ) First Mobile 3 T at Work PI: Valentin Fuster, Co-PI: Erling Falk, Peter Muntendam
HRP – BIOIMAGING – OMICS : EVALUATION & FU Randomization. Imaging vs Framingham Only Imaging N=6000 No Imaging Framingham N=1300 Imaging Risk US, CT, AAA, ABI Imaging Risk High (regardless FRS) CE-CTA or CE MRI (Carotid) N=2000 Imaging Risk Not High No Non CE MRI (Carotid, Aortic, Coronary) N=1000 Event Monitoring 3 Years Blood sampling PET-CT N=200
HSillesen, V Fuster, E Falk, P Muntendam 2010 (Sbm)
HSillesen, V Fuster, E Falk, P Muntendam 2009
ISCHEMIC STROKE HSillesen, V Fuster, E Falk, P Muntendam 2009 Also Other Non-Cerebral Events
3) US-NHLBI–IOM: Global CVD Prevention (Chair) Promoting CV Health 2010 – 2020 (Education) KNOWLEDGE 1. EPIDEMIOLOGY 2. ECONOMICS. RESPONSABILITY 3. COMMUNITY INCENTIVE 5. YOUTH Washington DC 4. INTERSECTORIAL 6. NEVER TOO LATE
400 350 300 250 -15% -20% -25% -30% 200 150 100 DM Lloyd-Jones, et al. , Circ 2010; 121: 586 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 0 2000 50 1999 Age-Adjusted Death Rates (per 100, 000) AGE-ADJUSTED DEATH RATES (PER 100000) DUE TO ALL CVDs AND STROKE – US – 1999 -2005
HML). Projected Deaths by Cause, 2004, 2015, 2030 R. Beaglehole et. al. Lancet 2008; 372: 1988.
Prevalence of CVD is increasing Treatment (Live Longer) and Technology ($) Rx, H-I Rx, L-I Rx, H-I $368 Bill, X 3 10 y MI, Pocket 80% $ 95% - Prev $ 5% V Fuster et. al. Nat Rev. Cardiol. 2009; 6: 669.
3) US-NHLBI–IOM: Global CVD Prevention (Chair) Promoting CV Health 2010 – 2020 (Education) KNOWLEDGE 1. EPIDEMIOLOGY 2. ECONOMICS. RESPONSABILITY 3. COMMUNITY INCENTIVE 5. YOUTH Washington DC 4. INTERSECTORIAL 6. NEVER TOO LATE
a) Bogota (n=6000), Madrid, Cardona (n=1200) Health, Drugs, Tolerance Randomized Study: End Points 1 Year – 10 Years
b) Cultural Habits –Grenada Project 1975 2000 High prevalence of hypertension - 28% > 140/90 mm Hg High prevalence of diabetes - 8. 5% > 126 mg/dl glucose
c) The Epidemic of CVD & The Law 1 4 x 2 x 3 Hypertension ?
d) Africa’s Ecological Zones & Initial 12 MV Sites UN & Earth Institute, NY V Fuster, S Sachs, R Vedanthan R. NHLBI / Rwanda Project, Jan 2009
The CNIC-Ferrer-MSSM Polypill ASA, Statin, ACE-Inhibitor 2 ary Prevention Project V Fuster, G Sanz , Nature Cardiov Med. 2007; 4: 173 Application 7º Programme Marco of the European Community
3) US-NHLBI–IOM: Global CVD Prevention (Chair) Promoting CV Health 2010 – 2020 (Education) KNOWLEDGE 1. EPIDEMIOLOGY 2. ECONOMICS. RESPONSABILITY 3. COMMUNITY INCENTIVE 5. YOUTH Washington DC 4. INTERSECTORIAL 6. NEVER TOO LATE
CNIC (Spain) - Discovering / Tutoring July 2009
It is Never too Late for Well Being Promotion of Physical & Mental Health AGE Tobacco, Exercise, Blood Pressure, BMI - Diet 20 30 40 50+ Each regular health care visit (or at least once every 2 years if BP < 120/80 mm Hg) Lipid Profile Every 5 years Blood Glucose test Every 3 years Clinical Breast Exam (CBE) and Mammography CBE q 3 yrs Pap test Yearly Colorectal Screening Prostate specific antigen test and/digital rectal exam ACS/ADA/AHA - Circ 2004; 109: 3244 Yearly CBE and Mammography Every 1 -3 years; depends on type of test and past results. Frequency depends on test preferred Offer yearly, assist informed decisions
Promoting CV & Mental Health: 2010– 2020 Science, Health, Education (SHE) Biological Clinical - From Atheroma to Aging – From CAD to DBD Population – From Risk to Health (3) (3)
Projected Annual Reductions in CV Events Given a Dietary Salt Reduction of 3 g per Day, According to Age Group K Bibbins-Domingo et. al. N Engl J Med. 2010; 362: 590 (UCSF)
Change in Rate/Prevalence from Baseline UNITED STATES: CHD – STROKE – 2004 -2008 0% 2004 2005 2006 2007 2008 -5% -10% -15% -20% -25% -30% -35% CAD Mortality High Blood Pressure DM Lloyd-Jones, et al. , Circ 2010; 121: 586 Stroke Mortality High Blood Cholesterol
CNIC (Spain) - Discovering / Tutoring July 2007
CNIC (Spain) - Discovering / Tutoring July 2008
TYPE 2 DIABETES, Hb. A 1 C, AND “U CURVE” In patients with type 2 diabetes, when using insulin secretagogues or insulin itself, today’s study does provide a rationale for an Hb. A 1 c threshold of 7. 5%, corresponding to the lowest death rate and lowest event rate for large-vessel disease. Priority should be given to insulin sensitisers for as long as possible in patients with type 2 diabetes, because these drugs allow a low Hb. A 1 c to be targeted without any risk of hypoglycaemia and its sequelae that could increase mortality (adrenergic drive & low K with arrhythmias, oxidative stress and inflammation, etc. ) CJ Currie et al. , Lancet 2010; 375: 486 Lancet 2010; 375: 438
Average Daily Salt Intake in Male and Female Americans, as Ascertained from 24 -Hour Dietary Recall, 2005– 2006 LJ Appel et. al. N Engl J Med. 2010; 362: 650 (John’s Hopkins)
The Uncaped Health Crusader of New York Michael Bloomberg • In 2008, he teamed up with Bill Gates in a US $500 million donation for global tobacco-control. 1 • He has campaigned against sugary drinks and trans fats in food. 2 • On Jan 11, he launched the National Salt Reduction Initiative that aims for a voluntary nationwide reduction of salt in packaged and restaurant foods. 3 Lancet 2010; 375: 25 – 1 JAMA 2010; 303: 357 – 2 JAMA 2010; 303: 553 3 JAMA 2010; 303: 448
WHO 2002 Report
Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction The AHA Strategic Impact Goal Through 2020 and Beyond Impact Goals: “By 2020, to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%. ” These goals will require new strategic directions for the American Heart Association in its research, clinical, public health, and advocacy programs for cardiovascular health promotion and disease prevention in the next decade and beyond. DM Lloyd-Jones, et al. , Circ 2010; 121: 586
Techniques for imaging the unstable plaque CM Matter, M Nahrendorf et. al. Eur Heart J. 2009; 30: 2566 Choudhury R, Fuster V, Fayad ZA Nature Rev. Drug Disc 2004; 3: 913. Jaffer FA et al. , Circ 2007; 116: 1052 - Sanz J et al. , Nature 2008; 451: 953. Mulder WJM , Fayad ZAet al. et. al. Nat CP Cardiov. Med. 2008; 5: s 103.
HEART MI BRAIN STROKE Thrombi 1) Emboli 2 2)Thrombi 3)Hemorrh Promoting CV & Mental Health 2010 – 2020
Health & Education - Human Population Growth In Developed & Developing Countries UN Population Division 2007 Estimated >65 yrs in 2020 - 690 million globally or 10% 460 million in developing countries Age Per Se Risk Factor ? or Age Cumulative Exposure To Risk factors ?
Longitudinal Modeling of Age-Related Memory Decline and the APOE 4 Effect APOE is a key constituent of VLDL and is vital to the transport of cholesterol and other lipids throughout the brain. Of the 3 alleles APOE 4 is the most prevalent risk factor for Alzheimer’s disease. We analyzed 815 subjects: 317 APOE 4 carriers (79 who were homozygous for the APOE 4 allele and 238 who were heterozygous) and 498 noncarriers. Longitudinal decline in memory in carriers began before the age of 60 years and showed greater acceleration than in noncarriers (P=0. 03), with a possible allele-dose effect (P=0. 008). Richard J. Caselli, et al. , NEJM 2009; 361: 255 (Arizona)
Locally Extensive - Effects of Simvastatin Uptake of [18 F]-FDG - Aortic Arch & Carotids in Humans 43 pts Tx 5 -20 mg simvastatin and diet for 3 months compared to diet alone N Tahara et. al. J Am Coll Cardiol 2006; 48: 1825 J HF Rudd , ZA Fayad. Nat Clin Pract Cardiovasc Med. 2008; 5: s 11 .
Systemic Carotid Disease – Calcium Score M Garcia, V Fuster, E Falk, P Muntendam 2009
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